The broad objective of this proposal is to examine the role of exercise in reducing the risk of lifestyle diseases. Metabolic syndrome risk factors are improved with weight loss, but most individuals regain the weight. Perhaps the negative health consequences of this weight regain can be eliminated with increased physical activity, which may help maintain the beneficial metabolic effects of weight loss. The primary aim of this study is to determine if exercise training is effective in maintaining metabolic syndrome parameters during weight regain. Our research hypotheses are: 1) Exercise training coupled with mild energy restriction will reduce risk factors associated with the metabolic syndrome. 2) Exercise training will maintain metabolic health following weight loss even if a portion of the weight is regained. In Phase 1, overweight men and women (N=100) with metabolic risk factors will be assigned to an individually prescribed dietary and supervised exercise weight loss program. The energy deficit will be prescribed and titrated in order to lose 10% of body weight over 6 months. In Phase 2, individuals will be randomly assigned to two weight regain groups for 4-6 months: 1) partial weight regain without exercise; 2) partial weight regain with exercise. Members of both groups will follow individual prescriptions of mild energy surplus (compared to weight loss energy) required to induce regain of 35-50% of the lost weight. Literature indicates that if unsupervised, individuals will regain this amount of weight within 1 year, but we propose to more systematically control the regain. According to pilot data, the recorded energy intake necessary for regain was similar to the background energy intake prior to the study. After the experimental regain trial, participants will be encouraged to re-lose the weight under supervision in an informal program. Metabolic syndrome parameters will be assessed at: 1) baseline, 2) post weight loss, 3) post weight regain. Outcome measures include: blood pressure, BMI, waist circumference, abdominal composition, thigh composition, insulin sensitivity, blood lipoproteins, inflammatory markers, and psychological variables. Data will be analyzed for each phase using a series of 1-way (weight loss hypothesis) and 2-way (weight regain hypothesis) MANOVA's with repeated measures and follow-up ANOVA's. Results of this novel experiment will help determine the value of exercise in maintaining a healthy metabolic profile and reduced disease risk even if weight is regained. These findings could provide additional stimulation for health care providers to recommend physical activity and also provide motivation to maintain an active lifestyle for millions of Americans who regain weight after weight loss. [unreadable] [unreadable]